The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (−0.97 cm², 95% confidence interval from −14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.

Objective: This study aims to investigate the correlation between serum uric acid levels and body fat distribution in patients with polycystic ovary syndrome (PCOS). Methods: Between May 2017 and March 2021, a total of 199 patients with PCOS were recruited from the Department of Endocrinology and Metabolism at the Shanghai Tenth People’s Hospital. Anthropometric characteristics, metabolic parameters, and reproductive hormones were measured. Hyperuricemia was defined as serum uric acid (SUA) greater than 420 μmol/l. Dual-energy X-ray absorptiometry (DEXA) was used to measure body fat distribution. Results: The prevalence of hyperuricemia in patients with PCOS was 28.64%. PCOS patients with hyperuricemia are more obese and have a higher waist-to-hip ratio (WHR) and worse lipid metabolism than those without hyperuricemia. According to SUA quartiles, patients in the highest quartile had higher total testosterone (TT), body fat accumulation, and lower sex hormone-binding globulin (SHBG) than patients in the lowest quartile. SUA was correlated with percentage of total body fat, arm fat mass, leg fat mass, trunk fat mass, android/gynoid (A/G) ratio, and visceral adipose tissue (VAT) mass. After controlling possible confounders, logistic regression analysis found that only excessive VAT mass could significantly increase the risk of hyperuricemia in patients with PCOS. Conclusion: In patients with PCOS, a high level of VAT mass, but not other fat compartments, will exacerbate the risk of hyperuricemia. Attention should be paid to the role of excessive VAT in the occurrence and development of PCOS with hyperuricemia.

Background: The causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis.Methods: The single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance weighted analysis, weighted-median analysis, weighted-mode analysis and Mendelian randomization-Egger regression analysis, supplemented by sensitivity analyses to validate the accuracy and robustness of the findings.Results: The IVW (OR = 1.23, 95% CI 1.06-1.43; P = 0.007) and weighted median (OR = 1.25, 95% CI 1.06-1.47; P = 0.009), along with sensitivity analysis validation, provide compelling evidence of a significant causal association between JIA and POF.Conclusion: The study revealed a significant causal association between genetically predicted JIA and POF, indicating that JIA significantly elevates the risk of developing POF. Therefore, it is recommended to implement screening for premature ovarian failure in women diagnosed with JIA.

More than half of polycystic ovary syndrome (PCOS) are overweight or obese. Environmental endocrine-disrupting chemicals (EDCs) are one of the important pathogenic factors in PCOS women. Methyl dihydrojasmonate (MDJ) is a food flavor additive, which can enter the body through several paths. However, the impact of MDJ on obese PCOS patients is still unknown. Hence, the study aims to determine whether MDJ may induce hallmarks of PCOS as new EDCs. The blood samples (33 obese PCOS patients and 30 controls) were collected for metabonomic sequencing. Sequencing results that serum MDJ level was significantly increased in obese PCOS patients, and was closely associated with the clinical phenotype of PCOS. C57BL/6J female mice fed high-fat diets were randomly divided into four groups. The PCOS model was established by subcutaneous injection of dehydroepiandrosterone for 21 days. Different concentrations of MDJ group were gavage of MDJ (60, and 120 mg/kg/d), and the control group was gavage of corn oil, once daily from pregnancy to offspring 16 weeks old. After 16 weeks, different concentrations of MDJ treatment resulted in an irregular estrus cycle and disturbed ovarian development in female mice. Serum TT and insulin resistance levels were increased in the MDJ group. At the cellular level, different concentrations of MDJ (50, and 100 μg/L) intervention mouse-primary-granulosa-cells (mpGCs) and measured supernatant TT levels after 48h. In the mouse ovarian tissue and mpGCs, we found that the expression of key genes for steroid synthesis (Star, Cyp17a1, Hsd3b1, Lhcgr) was increased significantly, while the expression of Cyp19a1 decreased after different concentrations of MDJ treatments. In preliminary experiments, we found that long-term exposure to MDJ during pregnancy and growth can induce PCOS phenotype in C57BL/6J female mice. Ongoing studies will determine how MDJ induces the hallmarks of PCOS and related mechanisms, which may help reveal the pathogenesis of PCOS. Disclosure: M.Cai: None. D.Dilimulati: None. Y.Zhang: None. X.Shao: None. S.Qu: None. M.Zhang: None. Funding: National Key R&D Program of China (2018YFC1314100); National Natural Science Foundation of China (81601269)